Assessing memory representations in freely-behaving animals with calcium imaging via miniscopes

对于这项RTI拨款，我们请求支持获得“最先进的”UCLA微型显微镜（版本4），以便在自由行为的啮齿动物中进行体内钙成像。这些微型显微镜将成为莱斯布里奇大学（UofL）加拿大行为神经科学中心（CCBN）新兴脑成像核心的重要补充。提议的成像设备将由至少9名nserc资助的CCBN系统神经科学家和一名来自UofL生物科学系的用户使用。所有用户都将获得使用该设备的权限和技术支持。加州大学洛杉矶分校系统的需求有以下几个原因：1)能够在动物自由活动时对大脑区域进行钙成像，如海马体（HPC），这是一项重大进步，增加了我们可以评估的功能范围；2)任务灵活；3)可用于不同的脑区；4)用户友好；5)它是该技术最有信誉的系统。

For this RTI grant, we request support to obtain “state of the art” UCLA miniscopes (version 4) to conduct in-vivo calcium imaging in freely behaving rodents. These miniscopes will be a crucial addition to our emerging Brain Imaging Core at the Canadian Centre for Behavioural Neuroscience (CCBN) at the University of Lethbridge (UofL). The proposed imaging equipment will be used by at least 9 NSERC-funded system neuroscientists from the CCBN, and a user from the Department of Biological Sciences at the UofL. All users will have access and technical support to use this equipment. The UCLA system is requested for several reasons: 1) ability to do calcium imaging in a brain area, like hippocampus (HPC), while the animal is freely-behaving is a major advancement that increases the range of functions we can assess; 2) it is task-flexible; 3) can be used in different brain regions; 4) it is user friendly; and 5) it is the most reputable system for this technique. The UCLA imaging system will be essential in several of our research programs including: 1) assess HPC representations formed during rapid new learning using the same or different spatial information which we hypothesize will differ in content and underlying neurobiological mechanism. The miniscopes will be used to determine how the representations differ under changed conditions; 2) investigate effects of circadian rhythm perturbations on HPC function. The miniscope will be used to assess the impacts of various forms of circadian perturbations (i.e./ shift work) on HPC representations; and 3) memory function in the mammalian brain appears to be organized by neural networks mediating different memory functions and within this organization, normal thought and behaviour arise from cooperative and competitive interactions between these systems. We will explore the mechanisms of interactions amongst multiple memory networks using the miniscopes to image activity in subcortical and cortical regions under different experimental conditions. Adding in-vivo calcium imaging using UCLA-V4 will be highly beneficial to our trainees because: 1) optical imaging methods are becoming increasingly popular over traditional electrophysiological methods for various reasons including large amounts of data can be collected and yet less technical expertise is required to run and maintain the equipment; 2) making sense of the high volumes of data collected from the miniscopes requires computational skills which our trainees will receive; and 3) enhance the quality of publications generated. All of these aspects will be advantageous to our trainees as they pursue a competitive space in neuroscience. We will use this technology to advance our knowledge of how behaviour is shaped by exposure to specific events, the neural networks responsible, and the biochemical mechanisms supporting these functions. Our research will benefit all Canadians as we expand our understanding of normal and abnormal behaviour.